Effect of Blueberries on Bone Turnover

Osteoporosis, Postmenopausal Clinical Trial

Official title:

Berries and Bones: The Effect of Polyphenolic Metabolites From Blueberries on Bone Turnover

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02630797
• Other study ID #: BB2015
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 12, 2017
• Est. completion date: August 2019

Study information

• Verified date: May 2018
• Source: Purdue University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study uses a bone labeling calcium tracer methodology to compare the dose-response effect of blueberry consumption on calcium retention and bone loss. Post-menopausal women will receive food or beverage products containing freeze-dried blueberries in the amount equivalent to 0.75 (low), 1.5 (medium), and 3 cups (high) of fresh blueberries per day over a 42-day period. The hypothesis is that the polyphenolics found in blueberries will reduce calcium loss from bones.

Description:

Participants will be dosed with Ca-41, a rare long-lived radioisotope of calcium. After the equilibration of tracer in the body and its deposition in bones (150 days), subjects will be randomized to one of 6 dose sequences, all of which will begin with a 42-day baseline period. During baseline, 24-hour urine will be collected every 14 days. Following baseline, subjects will enter a 42-day intervention period with one of three doses of blueberries equivalent to 0.75 (low), 1.5 (medium), and 3 cups (high) of blueberries per day. Each dose will be provided in the form of freeze-dried blueberry powder incorporated in 2-4 foods or beverages per day. During the intervention, 24-hour urine will be collected weekly for 6 weeks except week 1. After intervention, subjects will enter a 42-day washout period, during which 24-hour urine will be collected every 3 weeks. The entire study duration will be 444 days for subjects who have not been dosed with Ca-41 previously. In a crossover design, all subjects will complete three 42-day intervention periods corresponding to the three doses of blueberries (low, medium, and high), each followed by a 42-day washout period. The dose-response effect of continuous blueberry consumption over a 42-day period on bone resorption in healthy post-menopausal women will be studied by measuring the loss of Ca-41 in urine by Accelerator Mass Spectrometry.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: August 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 70 Years

Eligibility

Inclusion Criteria:

• Female subject is healthy

• Subject is > 4 years past the onset of natural menopause or total hysterectomy

Exclusion Criteria:

• History of metabolic bone disease or low trauma fractures;

• Subject taking osteoporosis treatment drugs or glucocorticoids within 6 months of the beginning of the study;

• Subjects taking bisphosphonates within 2 years of the beginning of the study;

• History of cancer, thromboembolisms, clotting disorders, uncontrolled hypertension, abnormal thyroid function, malabsorption syndrome, seizure disorders, or heart attack;

• BMI > 35 kg/m2;

• Subjects who will not comply with study interventions ;

• Subjects who will not stop taking natural product supplements of their own selection.

Related Conditions & MeSH terms

• Bone Loss, Age-related
• Osteoporosis
• Osteoporosis, Postmenopausal

Intervention

Dietary Supplement:
• Blueberry Baseline
Before the study beginning, eligible participants will receive a radioactive tracer, Ca-41, by iv infusion. A total of 150 days will be required for the equilibration of tracer in the body i.e. elimination from soft tissue and deposition in the bone. After equilibration, a baseline period of 42 days will occur, during which no blueberry products will be provided.
• Blueberry Low
One food or beverage product containing freeze-dried blueberry powder equivalent to 0.75 cups of fresh blueberries will be provided daily for 42 days.
• Blueberry Medium
Two food or beverage products containing freeze-dried blueberry powder equivalent to 1.5 cups of fresh blueberries will be provided daily for 42 days.
• Blueberry High
Four food or beverage products containing freeze-dried blueberry powder equivalent to 3 cups of fresh blueberries will be provided daily for 42 days.

Locations

Country	Name	City	State
United States	Department of Nutrition Science Purdue University	West Lafayette	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Purdue University

Country where clinical trial is conducted

United States, 

References & Publications (3)

Chen JR, Lazarenko OP, Wu X, Kang J, Blackburn ML, Shankar K, Badger TM, Ronis MJ. Dietary-induced serum phenolic acids promote bone growth via p38 MAPK/ß-catenin canonical Wnt signaling. J Bone Miner Res. 2010 Nov;25(11):2399-411. doi: 10.1002/jbmr.137. — View Citation

Devareddy L, Hooshmand S, Collins JK, Lucas EA, Chai SC, Arjmandi BH. Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis. J Nutr Biochem. 2008 Oct;19(10):694-9. doi: 10.1016/j.jnutbio.2007.09.004. Epub 2008 Mar 6. — View Citation

Weaver CM, Martin BR, Jackson GS, McCabe GP, Nolan JR, McCabe LD, Barnes S, Reinwald S, Boris ME, Peacock M. Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology. J Clin Endocrinol Metab. 2009 Oct;94(10):3798-805. doi: 10.1210/jc.2009-0332. Epub 2009 Jul 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ca-41 / Ca ratio in 24-hour urinary excretion to estimate calcium loss from bone	Urinary Ca-41 excretion will be expressed as Ca-41/Ca ratio, which is unit-less, and converted to a percent change from the baseline value.; 24-hour urine will be collected approximately every 2 weeks during baseline (week 0, 2, 4, and 6), weekly (except for week 1) during the low, medium, and high blueberry dose interventions completed in a randomized order (weeks 8-12, 20-24, 32-36) and every 3 weeks during the washout periods (weeks 15, 18, 27, 30, 39, 42). Ca-41/Ca ratios will be measured by Accelerator Mass Spectrometry.	From the beginning of baseline (week 0) to the end of the 3rd washout period (week 42)
Secondary	Fasting blood and urine analysis of blueberry polyphenolic metabolites	Polyphenol concentrations in urine and serum will be expressed in molar units and compared against reference values and across the study periods. Polyphenolic metabolites will be measured by LC-MSMS.; Fasting blood and urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42
Secondary	Serum and urine biochemical markers of bone metabolism: calcium concentration	Calcium concentration in urine and serum will be expressed in mg/L and measured by Atomic Absorption Spectrophotometry.; Fasting blood and urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42
Secondary	Serum biochemical markers of bone metabolism: Insulin Dependent Growth Factor-1 (IGF-1)	IGF-1 will be expressed in ng/mL and measured by ELISA.; Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42
Secondary	Serum biochemical markers of bone metabolism: Osteoprotegrin	Osteoprotegerin will be expressed in pmol/L and measured by ELISA.; Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42
Secondary	Serum biochemical markers of bone metabolism: RANK ligand	RANK-L will be expressed in pmol/L and measured by ELISA.; Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42
Secondary	Serum biochemical markers of bone metabolism: 25(OH) Vitamin D	25(OH) Vitamin D will be expressed in ng/mL and measured by LC/MS.; Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42
Secondary	Serum biochemical markers of bone metabolism: Sclerostin	Sclerostin will be expressed in ng/mL and measured by ELISA.; Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42
Secondary	Urine biochemical markers of bone metabolism: N-terminal telopeptide (NTX)	NTX will be expressed in ng/mL and measured by ELISA.; Fasting urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42
Secondary	Serum biochemical markers of bone metabolism: procollagen I intact N-terminal (PINP)	PINP will be will be expressed in ug/L and measured by ELISA.; Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).	Weeks 0, 6, 12, 18, 24, 30, 36, 42